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Addiction and Bipolar Disorder

Ana González-PintoIP CIBERSAM-G10

Hospital Santiago ApóstolUniversidad del País VascoCIBERSAM

SCHEME

EpidemiologyAnxiety, and alcohol and drug abusePolarity of episodes and alcohol and drug abuseUsing and quiting alcohol and drug abuse, and relation with outcomeTreating comorbidity Conclusions

Comorbid conditions: baseline data from STEP-BD

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Current SubstanceUse Treatment

Current NonalcoholSUD

Current Alcohol UD

Lifetime SUD

Simon NM et al.J Clin Psychopharmacol 2004; 24(5): 512Simon NM et al.J Clin Psychopharmacol 2004; 24(5): 512--20.20.

Pharmacotherapy and comorbidity in bipolar disorder

Substance use disorders in bipolar patients

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Current substanceuse treatment

Current nonalcoholSUD

Current alcohol UD Lifetime SUD

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• The STEP-BD trial examined the association between comorbidity and pharmacotherapy in patients with bipolar disorder

• A lifetime substance disorder was diagnosed in 48% of the sample; however, only 0.4% were receiving substance abuse- specific medications

• Use of ‘comorbidity-specific’ pharmacotherapy for anxiety disorders, substance use disorders, and attention deficit disorder was limited, suggesting comorbidity in bipolar disorder may be under-treated

Simon NM, et al. J Clin Psychopharmacol 2004;24:512-520SUD, substance use disorder; UD, use disorder

Alcohol abuse and gender in bipolar disorder

Frye MA, et al. Am J Psychiatry 2003:160;883-889

• Alcohol abuse was more prevalent in bipolar men than women at 49% vs 29%, respectively

Men Women

n=267 outpatients with bipolar disorder

• Relative risk for alcohol abuse compared with the general population was higher in bipolar women than men, with odds ratios of 7.35 vs 2.77, respectively

Men Women0

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Substance abuse in Mania: EMBLEM study data

Alcohol (25%)More compulsory admissionsMore rapid cyclingMore abuse of other substances

Cannabis (14%)Greater severityMore psychosisMore hospitalizationsMore compulsory admissionsMore abuse of alcohol and other substancesMore first episodes

EMBLEM. N=3536 manic patients across Europe. Haro et al, in 2006; Goetz et al, 2007; Vieta et al 2007.

Clinical characteristics of bipolar patients with versus those without substance and/or alcohol abuse

• More mixed episodes and rapid cycling• Slower recovery• More hospitalisations• Earlier age of onset• More suicide attempts• Increased aggressivity/criminality• Poor treatment adherence: 75% of non adherent

patients were substace users (González-Pinto et al, 2006)

Keller MB, et al. JAMA 1986;n. Vieta E, et al. Bipolar Disord 2001;. Colom F, et al. J Clin Psychiatry 2000;González-Pinto et al.,Bipolar Disord 2006

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Adherent

Substance abuse

Effect of compliance to lithium prophylaxis on bipolar disorder

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Married Women Suicidalacts

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• Up to 10 years of lithium prophylaxis demonstrated a 5.2-fold greater risk of suicide attempts among patients with poor compliance vs those compliant with treatment

• Non-adherence was significantly associated with:– Being male– Being unmarried– Having a history of comorbid

substance use– Having breakthrough episodes– Having psychiatric hospitalisation

Gonzalez-Pinto A, et al. Bipolar Disord 2006;8:618-624

** * *

* p≤0.002

• At 10 years, poor treatment compliance was significantly associated with risk of suicidal acts (p=0.016)

Predictors of suicide in patients with affective psychosis• The characteristics associated with suicide attempts in first-episode

patients with psychosis were assessed over 5 years

Suicide attempts p-value OR 95% confidence intervalInferior Superior

Male ns 0.857 0.129 5.674Previous suicide attempts ns 5.236 0.660 41.527

Alcohol abuse ns 1.307 0.225 7.606

Tobacco abuse ns 0.229 0.032 1.654

Cannabis abuse ns 0.532 0.063 4.463Stimulant abuse <0.05 7.239 1.412 37.107Age <0.05 0.884 0.790 0.989

• A total of 14.5% patients had suicidal behaviour; 2.4% died by suicide– 8-fold higher risk among patients with baseline stimulant abuse

González-Pinto A, et al. J Clin Psychiatry 2007;68:242-247ns, not significant

Reasons for comorbidity between bipolar disorder and substance abuse

Genetic diathesisGenetic diathesis with a common mediator (anxiety)Common neurobiological mechanisms (dopamine, etc.)Overlap of diagnostic criteriaSocial diathesisSelf-medicationTreatment side-effectsInduction of mania or depression by substances

Vieta E, presented at the IX Symposium on Bipolar Disorders, Barcelona, Spain, Januar

Comorbid anxiety disorders in bipolar patients with alcohol and substance use

Anxiety disorders are more common in bipolar disorder patients with alcohol abuse vs patients with cocaine abuse2

Patients with early onset anxiety disorders have an increased lifetime prevalence of bipolar disorder3

1. Mitchell JD, et al. J Affect Disord 2007;102:281-2872. Goldstein BI, et al. J Affect Disord 2007;103:187-195

Antidepressant-induced mania in bipolar patients with substance misuse• Patients with bipolar disorder were interviewed to investigate the

relationship between psychoactive substance use and mania

• Patients with a history of substance abuse and/or dependence had a significantly greater risk of mania than those with no such history (OR=6.99, p=0.007)

Reproduced with permissionGoldberg JF, Whiteside JE. J Clin Psychiatry 2002;63:791-795

Variable Present Absent p-value

Female, n (%) 12/21 (57.1) 19/32 (59.4) 1.000Age at illness onset, mean years (SD) 20.7 (11.9) 18.1 (8.8) 0.532

Comorbid substance abuse/dependence, n (%) 12/20 (60.0) 5/28 (17.8) 0.005

Depressed polarity at first episode, n (%) 19/20 (95.0) 22/27 (81.4) 0.221

Bipolar II, n (%) 8/19 (42.1) 10/25 (40.0) 0.887Antidepressant trials/year, estimated mean (SD) 0.20 (0.14) 0.12 (0.10) 0.041Bipolar family history, n (%) 10/18 (56) 10/22 (46) 0.525

A new specifier: Predominant polarity

Depressive polarity60% bipolar patientsMore bipolar IIMore depressive onsetMore seasonal patternMore suicide attemptsBetter long-term response to lamotrigineMore antidepressant use

Manic polarity40% bipolar patientsMore bipolar IMore manic onsetYounger and earlier onsetMore substance misuseBetter long-term response to atypical antipsychotics

Colom F, Vieta E, Daban C, Pacchiarotti I, Sánchez-Moreno J. Clinical implications of predominant polarity in bipolar disorder. J Affect Disord, 2006.

Polarity is also related to tretament

Ten years follow-up of 169 bipolar patients. Depressive polarity:

More relapses.More hospitalizations.More suicide attempts

More difficulties in quitting .

González-Pinto y cols., J Affect Dis 2009

González-Pinto y cols., J Affect Dis (2009)

González-Pinto y cols., J Affect Dis 2009

LONG TERM IMPROVEMENT AFTER CANNABIS WITHDRAWAL

G Pinto et al. Schizophrenia Bull., 2009

Lithium for adolescent bipolar disorders with secondary substance dependency

• 25 adolescent patients with bipolar disorder and SSD received lithium or placebo • Randomised, double-blind, placebo-controlled pilot study

• Addiction to both alcohol and cannabis was the most frequent category of SSD• The mean scheduled weekly serum lithium level of active responders was

0.9 mEq/L • Lithium treatment significantly improved:

• Psychopathology measures• Weekly random urine drug assays

• The mean 6-year interval between the onset of BD and onset of SDD strongly suggested that early recognition of BD may enable effective prevention of comorbid substance dependency

Geller B, et al. J Am Acad Child Adolesc Psychiatry 1998;97:171-178BD, bipolar disorder; SDD, substance dependency disorder

Add-on valproate semisodium in bipolar I disorder with alcohol abuse

n=59, 44 male, mean age 38 yearsRecently detoxedBRMS 15.3, HRSD-25 20.8All received lithium; valproate semisodium vs placebo added for 24 weeksValproate semisodium improved % heavy drinking days, drinks per heavy drinking day (HD), time to relapse

Salloum IM, et al. Arch Gen Psychiatry 2005;62:37-45

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Heavy drinking days (%)

No. drinks per HD

Days to relapse

Lithium + placeboLithium + valproate semisodium

BRMS, Bech-Rafaelsen Mania Scale; HRSD-25, Hamilton Rating Scale for Depression

ValproateBoth groups improved equally on mania and depression scoresCompared with placebo group. Divalproex (valproate) group had

Fewer heavy-drinking daysFewer drinks per heavy-drinking dayFewer drinks per drinking day

Outcome was correlate with complianceDivalproex group had better liver function test scores

Salloum IM et al. Arch Gen Psychiatry 2005; 62(1): 37-45.

Efficacy of naltrexone in patients with bipolar disorder and alcoholism• A 16-week, open-label pilot study was conducted to assess the effect

of naltrexone in patients with bipolar disorder and alcohol dependence • Assessments included:

• 17-item Hamilton Rating Scale for Depression (HRSD-17)• Young Mania Rating Scale (YMRS)• Brief Psychiatric Rating Scale (BPRS)• Alcohol craving scale

• Significant improvement observed in HRSD-17, YMRS and days of alcohol use and craving

• Other drugs tried in small, open label studies for bipolar disorder with substance abuse, include gabapentin, lamotrigine, quetiapine and aripiprazole

Brown ES, et al. Depress Anxiety 2006;23:492-495

Group therapy for bipolar disorder and substance dependence

A RCT assessed integrated group therapy (addresses the two disorders simultaneously) vs group drug counselling (focused on substance use)

62 patients with bipolar disorder and current substance

Intention-to-treat analysis showed:

Significantly fewer days of substance use for integrated group therapy vs drug counselling during treatment and follow-up

Number of weeks ill with bipolar disorder during treatment and follow-up similar in both groups

More depressive and manic symptoms in integrated group therapy patients vs drug counselling patients

Data suggest that integrated group therapy is a promising approach to reduce substance use in patients with bipolar disorder

Weiss RD, et al. Am J Psychiatry 2007;164:100-107RCT, randomised controlled trial

J Clin Psychiatry 2000; 61: 361J Clin Psychiatry 2000; 61: 361--367.367.

Am J Psychiatry 2007; 164:100–107.

Group Therapy

Population21 adults received integrated group therapy24 adults received usual care

Integrated group therapy was associated withSignificantly (p<0,02) greater decrease in Addiction Severety Index drug and alcohol composite scoresHigher probability of longer (at least 2-month or 3-month) periods of abstinence

Conclusions

The prevalence of substance use disorders is very high in patients with bipolar disorderSubstance use comorbidity carries worse outcome of bipolar disorderBipolar patients with substance misuse have higher suicide risk and less adherence to treatmentAnxiety is frequently a mediator between alcohol and drug abuse and bipolar disorderTreatment of anxiety is crucial, but antidepressants are associated with induced mania in BD with comorbid SUD

Conclusions

Evidence-base for treatment is limited, but withdrawal improves dramatically outcome in the long, but not in the short-term.Valproate, lithium, and naltrexone can be used to treat bipolar patients with substance use disordersPsycoeducation and psychosocial interventions are crucial for patients with comorbidity

CHRISTMAS LUNCH